US 12,453,706 B2
Bispecific stealth lipid nanoparticle compositions for cell targeting
Debra Klatte, Cambridge, MA (US); Lalita Oonthonpan, Cambridge, MA (US); Viktoriya Syrovatkina, Cambridge, MA (US); Anthony Joseph Perniciaro, Cambridge, MA (US); Salma Merchant, Cambridge, MA (US); and Brandon Michael Johnston, Cambridge, MA (US)
Assigned to Generation Bio Co., Cambridge, MA (US)
Filed by Generation Bio Co., Cambridge, MA (US)
Filed on Feb. 24, 2025, as Appl. No. 19/061,632.
Application 19/061,632 is a continuation of application No. PCT/US2024/052260, filed on Oct. 21, 2024.
Application PCT/US2024/052260 is a continuation in part of application No. PCT/US2024/032646, filed on Jun. 5, 2024.
Application PCT/US2024/052260 is a continuation in part of application No. PCT/US2023/082078, filed on Dec. 1, 2023.
Claims priority of provisional application 63/705,914, filed on Oct. 10, 2024.
Claims priority of provisional application 63/645,650, filed on May 10, 2024.
Claims priority of provisional application 63/642,445, filed on May 3, 2024.
Claims priority of provisional application 63/562,079, filed on Mar. 6, 2024.
Claims priority of provisional application 63/545,474, filed on Oct. 24, 2023.
Prior Publication US 2025/0186358 A1, Jun. 12, 2025
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 9/00 (2006.01); A61K 9/51 (2006.01); A61K 47/68 (2017.01); A61K 47/69 (2017.01); C07K 16/28 (2006.01); C12N 15/88 (2006.01)
CPC A61K 9/5123 (2013.01) [A61K 9/5146 (2013.01); A61K 47/6849 (2017.08); A61K 47/6929 (2017.08); C07K 16/2809 (2013.01); C07K 16/2896 (2013.01); C12N 15/88 (2013.01); C07K 2317/569 (2013.01); C07K 2317/622 (2013.01)] 30 Claims
OG exemplary drawing
 
1. A stealth lipid nanoparticle (LNP) comprising:
(a) a therapeutic nucleic acid (TNA);
(b) an ionizable lipid;
(c) a sterol;
(d) a first lipid-anchored polymer comprising a first hydrophilic polymer and a first lipid-linker, wherein the first lipid-linker comprises a first lipid comprising at least two hydrophobic tails, and wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C18);
(e) a second lipid-anchored polymer comprising a second hydrophilic polymer, a second lipid-linker, and a first reactive moiety conjugated to a first targeting moiety; wherein the second lipid-linker comprises a second lipid comprising at least two hydrophobic tails, wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C18); and wherein the targeting moiety is a variable heavy chain-only antibody (VHH) or a single-chain antibody (scFv); and
(f) a third lipid-anchored polymer comprising a third hydrophilic polymer, a third lipid-linker, and a second reactive moiety conjugated to a second targeting moiety; wherein the third lipid-linker comprises a third lipid comprising at least two hydrophobic tails, wherein each hydrophobic tail comprises a carbon chain having 18 carbon atoms (C18); and wherein the second targeting moiety is a variable heavy chain-only antibody (VHH) or a single-chain antibody (scFv);
wherein the first targeting moiety and the second targeting moiety are different;
wherein the first targeting moiety and the second targeting moiety are each cell-type specific targeting moieties, wherein the cell-type is a hematopoietic stem cell (HSC),
wherein the molecular weight of each of the second and third hydrophilic polymers is greater than the molecular weight of the first hydrophilic polymer;
wherein the first lipid-anchored polymer, the second lipid-anchored polymer, and the third lipid-anchored polymer are present at a combined molar percentage of about 2% to about 5%, and wherein the second lipid-anchored polymer and the third lipid-anchored polymer are present at a combined molar percentage of about 0.01% to about 0.5%; optionally wherein the stealth LNP comprises about 5 to 400 total targeting moieties.